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Doctor Sarah Cassidy has been working at Arkham while assigned to the case of serial killer Victor Zsasz. She was stalked and targeted by Zsasz after his most recent escape. Sarah has also studied and interviewed another infamous inmate at Arkham, Warren White. Cassidy is good friends with Doctor Gretchen Westler, another Arkham doctor. She lives alone in a Gotham apartment with her cat, maintaining a good relationship with her best friend, Garianne. Cassidy works the night shift at Arkham's Medical Facility during the fourth week of every month.

Doctor Cassidy was among the many doctors present during the Joker's takeover of Arkham Asylum. An army of Blackgate convicts temporarily housed in Arkham broke free and seized Arkham West, led by the Joker and Harley Quinn. Cassidy was oblivious to the situation outside the Medical building. She was in working in her office in the Medical Facility's Sanatorium when armed Blackgate convicts led by Quinn burst in, under orders from the Joker to capture all the doctors working there. They shot the asylum guards in the Upper Corridor and killed several medical staff while rounding up two orderlies and another doctor. They dragged Doctor Cassidy out of her office and into an adjoining room while Harley Quinn proceeded to the Medical Facility with a captured police Commissioner Gordon, who had been at Arkham to supervise the Joker's transferral, in tow.

Cassidy attempted to resist her assailants but they held her at gunpoint. Doctor Cassidy reluctantly complied with them while holding back tears. Discouraged in the face of the impending situation, she cried quietly in a corner as the Joker's men strapped two orderlies into electroshock chairs to prevent escape.

As the convicts stood guard, Batman found a way into the Medical Facility upon arriving from Arkham East. He contemplated why the Joker would want all the doctors and gained access to the Sanatorium through a ventilation shaft in the Maintenance Access. Batman defeated the convicts holding the doctors prisoner and approached Sarah. She explained she was carrying out her normal duties when armed thugs had come in and captured her. She and another doctor explained they had heard gunfire from the Upper Corridor, and that Doctor Adrian Chen had gone to the Surgery Room, Doctor Steve Kellerman had gone to Patient Observation, and Doctor Penelope Young had gone to the X-Ray facility. Batman advised the doctors to remain in the Sanatorium before leaving to search out the other doctors. Doctor Cassidy set to work freeing an orderly in one of the electroshock chairs. After she and another doctor had freed the orderlies, they examined one of the convicts Batman had defeated earlier while awaiting his return. When Batman returned with security guard Aaron Cash and Doctor Young, he found that the elevator was bringing someone up from Secure Access. He left Doctor Young with Cash to go retrieve her notes in the Arkham Mansion, and ordered Cassidy to go to the Patient Observation Room with the orderlies and barricade herself inside. Cassidy left the Sanatorium, and followed Batman's instructions. She regrouped in the Patient Observation Room with Doctor Kellerman, and the two doctors helped seal off the room with large pieces of furniture, mainly cabinets and desks.

Doctor Cassidy remained in the Patient Observation Room, conversing in low tones with Doctor Kellerman for the remainder of the Joker's takeover, which ended as Arkham's remaining security forces and the Gotham City Police Department retook control of Arkham island. Cassidy survived the attack on Arkham and returned to her duties after the Joker was placed back in custody. It is unknown if she met her former patient, Zsasz, during the takeover, as he had been freed from his cell during the chaos.